Toxic side effects on non-routinely monitored organs at risk following definitive radiotherapy for locally advanced cervical cancer: a narrative review

The standard-of-care treatment for locally advanced cervical cancer (LACC) comprises external beam radiotherapy (EBRT) combined with brachytherapy (BT) and concurrent platinum-based chemotherapy. The development and refinement of brachytherapy techniques have enhanced local tumour control and survival outcomes in cervical cancer patients. However, this treatment modality is also associated with considerable toxic effects. Toxicities affecting the ureters, urethra, vagina, and other organs occur less routinely monitored in routine clinical practice. As a result, when these toxicities develop, they frequently present as severe complications that cause considerable patient distress, significantly impair quality of life, increase therapeutic complexity, and may even become life-threatening. This comprehensive narrative review synthesizes and discusses the current evidence on radiation-induced toxicities affecting organs and tissues beyond the bladder and major gastrointestinal structures, including the rectum, small bowel, and sigmoid colon in patients with LACC undergoing definitive radiotherapy. Particular emphasis is placed on toxicity profiles, reported incidence, current contouring practices, dose-response relationships, clinical outcomes, and management strategies. Current management of these OARs presents several critical challenges: the absence of consensus regarding contouring methods, limited evidence on dose-effect relationships, and a lack of standardised guidelines for delineation approaches, dosimetric parameter selection, and definitive dose constraints. To address these limitations and improve patients’ long-term quality of life, future research should prioritise international multicentre collaborations and the development of large-scale prospective databases. Such initiatives would enable comprehensive dose modelling and validation studies. Overcoming the current shortcomings in contouring standards, dose constraints, toxicity assessment, and prevention strategies would not only optimise individualised treatment planning and reduce the risk of severe complications, but also advance precision radiotherapy to towards more sophisticated and individualized treatment strategies.